Gastroduodenal Stress
Ulceration
Bryan Woolridge
POS Rounds
29 October 2003
Objectives
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Define entity
Etiology
Differentiation of UGI ulcers
Pathophysiology
Identify population at risk/risk factors
Clinical presentation and diagnosis
Prevention and treatment/prognosis
Research and practice guidelines
Definition
• Multiple shallow erosions in the stomach
and/or duodenum secondary to severe and
unremitting physiologic stress that tend to
cause hemorrhage but not perforation
• The GI component of multi-organ failure
Etiology
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Shock
Sepsis
CNS tumors/trauma
Burns
Multi-trauma
Differentiating stress ulcers
• Stress ulcers
• Variants
– Cushing’s ulcers
– Curling’s ulcers
Differentiating stress ulcers
• Stress ulcers
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Shallow discrete lesions but can coalesce
Congestion and edema
Little inflammatory reaction at the margins
Predilection for parietal mucosa
Duodenal involvement 30%
Sometimes both
Differentiating stress ulcers
• Cushing’s ulcers
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2° to CNS trauma
↑ vagal activity from ↑ ICP
High acid output and ↑ circulating gastrin
Solitary
Morphologically similar to ordinary
gastroduodenal ulcer
– Tendency to perforate
Differentiating stress ulcers
• Curling’s ulcer
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2° to thermal injuries/burn victims
↑ gastric secretions
Perforation more common than stress ulcers
May be anywhere along GI tract
Pathophysiology
• Pathogenesis
– Acute in onset
– Multiple in number but can coalesce
– Commonly located in proximal stomach
– Not associated with hypersecretion of acids
– Failure of cytoprotective factors
Pathophysiology
1. ↓ gastric blood flow/mucosal ischemia
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↓ supply of blood buffers
↓ neutralization of H+ ions
2. ↓ mucosal resistance
– Circulating toxins
– ↓ mucosal renewal
– ↓ production of endogenous prostanoids
– Thinning of surface mucus layer
– ↑ corticosteroid secretion/administration
– Bile reflux
– Drug exposure (ASA,NSAIDS)
Pathophysiology
• Gastric protection
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Mucus secretion
HCO3- secretion
Epithelial restitution
‘Alkaline tide’ that neutralizes acid
Energy mismatch when metabolic demand of acid
secretion not met with sufficient blood flow
• None appears to contribute to stress ulceration
• ↓ blood flow is major factor
Pathophysiology
3. ↑ back diffusion of H+ and subsequent acidinduced injury
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? Relation to acid hypersecretion
Theory is disputed
Formation of ulceration is function of:
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Rate of decline in intramucosal pH
Absolute intramucosal pH
Duration of intramucosal pH outside normal limits
Pathophysiology
– Animal model:
• Neutralization of pH - ↓ stress ulceration
– ↑ acid secretion with stress
• No evidence that ↑ acid secretion in ulceration area
– ↑ acid secretion in burn & CNS trauma victims
• More common to manifest as serious bleeding
• More benign in other etiologies of stress ulcers
• Neutralization of pH does not prevent ulceration
Pathophysiology
– Back diffusion seen in less than ½ of patients
– Mucosal damage in absence of acid
– Rx neutralization of acids – modest results
• ? Acids only have a modest role
– Acid does play a role – extent unknown
– ? Effect rather than a cause
Population at risk
• UGI bleed from stress ulceration
– ICU – 5%
– Severe trauma – 20%
– Burns (>35% TBSA) – up to 50%
Risk factors
• Risk Factors
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Etiologic factor present
Large transfusion requirements
ARDS
Ventilator > 48 hr
ICU > 1 week
Oliguric renal failure
Post-traumatic hepatic dysfunction
Coagulopathy (complications moreso than cause)
High dose steroids
Natural History
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Precipitating insult
Superficial mucosal erosion
Progression and coalescence (20% if untreated)
Overt bleeding (3-5 d post insult)
Clinically important bleeding (4-5 d post insult)
Anemia and hypovolumia
• All bleeding stops eventually
Natural history
• Overt bleeding
– Hematemesis, bloody gastric aspirate
– Melena
– Hematochezia
Natural history
• Clinically significant bleeding
– Overt bleeding +
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↓ BP 20 mmHg in 24 hr
↓ BP 10 mmHg + ↑ HR 20 on orthostatic change
↓ Hgb 20 g/L + transfuse 2U blood in 24 hr
Requiring surgery
Clinical presentation
• Precipitating insult – asymptomatic (GI)
– Within 24-48 hr: >60% have erosions
• UGI bleed ~ 20% of susceptible patients
– Painless hematemesis (NG tube aspirate)
– Melena/hematochezia – uncommon initial
presentation
– Clinical onset of hemorrhage 3-5 d post insult
– Massive bleeding 4-5 d post insult
Clinical presentation
• Perforation
– 10% of cases (not initial presentation)
• Manifestations of etiology
– Shock, sepsis, burns, CNS, multi- trauma
– Deteriorating vital signs – hypovolumia
– Autopsy
Diagnosis
• H&P
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Risk factors
Precipitating insult causing stress
Vital signs – hypovolumia
Stool for occult blood
• Index of suspicion
– critically ill patient with painless UGI bleed
– Presence of risk factors
Diagnosis
• Barium swallow
– Inaccurate because superficial in nature
• Arteriography
– Not 1st line
• Endoscopy
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Correctly identify bleeding source in 90%
Erosions 24-48 hr post insult
Subclinical diagnosis
? Coag or diathermy – diffuse process
Treatment
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Resuscitation
Control of hemorrhage
Prevention of recurrence
Patient survival – underlying cause
Treatment
• ABCs
– Resuscitation (Burn victim - 3cc/kg/%TBSA)
– Restore circulating blood volume
– Restore cardiac output
• IVF, blood, clotting factors
– Aggressive monitoring
• Art line, Swan-Ganz, ins and outs
• Treat underlying cause
– Ulceration is superficial – resolve with removal of
etiology
• Correct acid-base imbalance
Treatment
• Prevention
– Prophylaxis
• Reduce amount of intraluminal acid
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Intragastric antacid (titrate pH > 3.5-4)
H2 blockers
PPI
sucralfate
– Early institution of feeding reduces incidence
– TPN patients seem to be protected – No benefit from
H2 blockers in this group
– Avoid surgery if possible
Treatment
• Studies of cimetidine vs. intragastric antacid
– pH > 3.5
• Antacid better irrespective of cimetidine dosage
– Bleeding
• 2-18% with cimetidine
• 0-5% with antacid
– Endoscopic
• No difference in mucosa
Treatment
• Why cimetidine fail?
– Inadequate drug delivery
– ↓ secretion but ↓ buffer
– ? Importance of ↓ acid secretion in stress ulcers
Treatment
• Gastric lavage with chilled solutions
– Combat sepsis
• H2 blockers
– not effective for treating active bleeding
– ↓ rate of rebleed
– ↓ acidity – theoretically ↑ risk nosocomial pneumonia
• Not supported by experience
• Some success with vasoconstrictors
– percutaneous vasopressin into Left gastric artery
– Before surgery
Treatment
• Surgery
– Vagotomy and drainage
– Vagotomy and pyloroplasty – ? treatment of choice
• With oversewing of bleeding areas
– Vagotomy and extensive subtotal gastrectomy
• With oversewing of bleeding areas
– Total gastric devascularization
– Total gastrectomy – if needed for extent of ulcers
• Inadvisable if other option due to ↑ operative mortality
Treatment
• Vagotomy
– Reduce gastric secretion
– Favors opening of AV shunts
• Divert blood from engorged mucosa
Prognosis
• Dependent on etiology and PMHx of patient
• Mortality
– 30-40% in any circumstance
Research
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Many studies in literature
Different patient populations
Different clinical problems
Different outcomes
– Some clinically insignificant
Research
Cook et al.
– 269 studies of stress ulcer prophylaxis
– 63 comparable and included in meta-analysis
• H2 Blockers
– ↓ overt bleeding
– ↓ clinically important bleeding
• sucralfate
– ↓ overt bleeding
– Insufficient data on clinically significant bleeding
– Less pneumonia and better overall survival than other
regimens
Research
Cook et al. – also prospective multicentre
study on risk factors for clinically
significant GI bleeding in ICU patients
– Incidence low – 33/2252 (1.5%)
– Risk factors
• Coagulopathy
• Ventilation > 48 hr
Practice guidelines
• ? How we judge bleeding as significant
– Endoscopic evidence with no occult blood
– No overt bleeding
• Therapy doesn’t change outcome
• Potential unnecessary side effects
• $$$
– Clinically significant bleeding
• Incidence low
• Treat those with risk factors
Practice guidelines
American Society of Hospital Pharmacists
• Prophylaxis provided for:
– Ventilated > 48 hr
– ICU with coagulopathy
– Hx of GI ulceration or bleeding 1 year prior to
admission
– 2 or more or the following risk factors
• Sepsis, ICU > 1 week, occult bleeding > 6 days,
high dose steroids (>250 mg hydrocortisone or =)
Practice guidelines
• Prophylaxis recommended for:
– ICU with GCS ≤ 10 or inability to obey simple
commands
– Thermal injury > 35% TBSA
Practice guidelines
• Prophylaxis beneficial for:
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Partial hepatectomy or liver failure
Multi-trauma
Spinal cord injuries
Transplant patients
• Patients not in ICU do not benefit from
prophylaxis
Practice guidelines
• Studies supporting these recommendations show
– ↓ clinically significant bleeds with H2 blockers and
sucralfate
– Insufficient data for efficacy of PPI or misoprostol
– Measuring gastric pH does not help manage the
problem
– Major complication is pneumonia
• Not supported by experience
Conclusion
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Very high morbidity and mortality
High index of suspicion in patients at risk
Aggressive resuscitation
Prophylaxis
– H2 receptor blockade
• Treat underlying cause
– Ulcerations are superficial and reversible
References
• Essentials of Surgery
– Sabiston (1987)
• Principles and Practice of Surgery
– Forest, Carter, MacLeod (1991)
• Current Surgical Diagnosis and Treatment
– Way and Doherty (2003)
• Surgery: Basic Science and Clinical Evidence
– Norton, et al. (2001)